Vibrio alginolyticus is a Gram-negative pathogen of both marine animals and humans, resulting in significant losses for the aquaculture industry. Emerging evidence indicates that V. alginolyticus manipulates cell death for its pathogenicity, but the underlying molecular mechanisms remain unclear. Here, a gene designated vopS in V. alginolyticus HY9901 was identified, which was predicted to encode the T3SS effector protein. To determine whether VopS contributes to the pathogenesis of V. alginolyticus, the ΔvopS mutant strain was constructed and phenotypically characterized. The deletion of VopS not only reduced the ability to secrete extracellular proteases and virulence but also affected the expression of the T3SS genes. Furthermore, VopS was cytotoxic and induced apoptosis, as confirmed by elevated LDH and the activation of caspase-3. Metabolomic analysis revealed considerable metabolomic disruptions upon V. alginolyticus infection. The VopS effector induced host cell ferroptosis by promoting the synthesis of adrenic acid, depleting cellular glutathione, and subsequently increasing the accumulation of ferrous (Fe²⁺). Taken together, our findings provide that the VopS effector is an essential virulence factor of V. alginolyticus, which can lead to ferroptosis.

Spring viremia of carp virus (SVCV) is a significant pathogen that has notably hindered the advancement of cyprinid aquaculture in recent years. Infections caused by SVCV are often associated with substantial economic losses due to the absence of effective treatment options. Previous reports indicated that N-(4-methyl-2-oxo-2H-chromen-7-yl) benzenesulfonamide (N6) exhibits inhibitory effects on SVCV proliferation. This study aims to comprehensively evaluate the anti-SVCV effects of N6 using healthy young carp as the experimental model. The research investigates the antiviral activity of this compound in vivo, the immune response of interferon (IFN)-related genes, its impact on the horizontal transmission of SVCV, and histopathological changes. The results indicate that N6 significantly inhibits SVCV infectivity and apoptosis in EPC cells in vitro. Furthermore, while N6 reduced horizontal transmission of SVCV in a static cohabitation challenge model, the N6-treated SVCV-infected group showed a nearly 3-fold decrease in viral load compared to the control group, it did not completely prevent transmission at established antiviral dosages. Histopathological analysis of the affected fish revealed that N6 effectively mitigated tissue damage induced by SVCV. Additionally, the up-regulation of six IFN-related genes suggests that N6 may indirectly activate IFNs to facilitate the clearance of SVCV in the kidney and spleen, as demonstrated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). These findings provide a foundation for further investigations into the mechanisms by which N6 acts against SVCV and may aid in the development of novel anti-SVCV therapeutics.

Nocardia seriolae infection poses a serious threat to largemouth bass (Micropterus salmoides) aquaculture, owing to the lack of effective control strategies. This study investigated the antibacterial effects and underlying mechanisms of Macleaya cordata alkaloids—sanguinarine (SE) and chelerythrine (CHE)—against N. seriolae through integrated physiological and transcriptomic approaches. Results showed SE and CHE exhibited strong in vitro antibacterial activity, with minimum inhibitory concentrations (MICs) of 62.5 and 7.8 μg/mL, respectively. In vivo trials revealed that dietary supplementation with either alkaloid significantly enhanced the survival of infected fish, yielding relative percent survival (RPS) values of 34.5% for SE and 40.0% for CHE. Concurrently, both treatments reduced bacterial load and alleviated granulomatous pathology in multiple organs, including the liver, spleen, and kidney. Physiological analyses revealed severe damage to the cell envelope, as evidenced by increased membrane permeability and structural disintegration observed under transmission electron microscopy (TEM). Transcriptomic profiling identified 3708 and 5095 differentially expressed genes (DEGs) in the SE- and CHE-treated groups, respectively, with notable downregulation of key genes involved in peptidoglycan biosynthesis, the citrate cycle, oxidative phosphorylation, and the pentose phosphate pathways. These findings demonstrate that SE and CHE inhibit N. seriolae through a multi-target mechanism simultaneously disrupting cell envelope integrity and energy production, laying the groundwork for their development as eco-friendly aquaculture therapeutics.